23andMe, Inc., is a personal genomics company with a mission of accelerating medical discoveries by empowering consumers to participate in research. At the heart of this mission is the 23andMe research engine, a novel platform for conducting genetic studies that allows individuals to participate in genetic research by enrolling in the company's Personal Genome Service(R) and taking online surveys. Over 130,000 individuals have contributed genetic and phenotypic data, and this number is growing by over 50,000 each year. Our initial publications have shown the power and efficiency of this web-based approach for discovering novel genetic associations for a range of traits and diseases. These early successes, however, made only partial use of the rich and rapidly expanding 23andMe database. Our current challenge is to fully mine the genetic and phenotypic information that we are collecting in order to accelerate the pace of human genetic research. In Phase I of this grant, we have demonstrated the feasibility of this unique research approach. We have developed new computational tools to facilitate analysis of thousands of phenotypes in hundreds of thousands of people, curated survey data related to many new phenotypes, studied the reliability of our genetic data, and conducted user interviews for several surveys. Building on this foundation, in Phase II we will refine existing survey questions, develop and post new surveys, and analyze a subset of the resulting data to further demonstrate the utility of this platform (Aim #1); implement novel web-based data collection tools to efficiently gather longitudinal and cognitive data (Aim #2); capitalize on the upcoming explosion of whole-genome sequence data through statistical imputation, making it possible for us to discover rare SNPs associated with disease (Aim #3); and test and refine a new tool, the 23andMe Research Portal, that will provide external researchers access to the 23andMe database (Aim #4). We expect that by the end of the proposed project the 23andMe database will include genetic and phenotypic data for over 400,000 individuals, including members of several understudied populations. This database has the potential to yield thousands of novel genetic associations for diseases and traits, leading to a greater biological understanding of these conditions, potential drug targets, and improved tools to predict an individual's genetic risk of disease. A key commercial outcome of the project will be a database and research engine that is more valuable to potential research partners. Furthermore, discoveries will drive new reports for 23andMe customers, thus increasing the value of the Personal Genome Service(R).